tbuckley/cabot-search huggingface dataset:
Safety and Short-term Outcomes of High-Dose Erythropoietin in Preterm Infants With Intraventricular Hemorrhage
Authors: Sven Wellmann, Cornelia F. Hagmann, Stefanie von Felten, Leonard Held, Katrin Klebermass-Schrehof, Anita C. Truttmann, Claudia Knöpfli, Jean-Claude Fauchère, Christoph Bührer, Hans Ulrich Bucher, Christoph M. Rüegger, Philipp Meyer, Gabriel Konetzny, Corinne Däster, Sven M Schulzke, Severin Kasser, Roland Gerull, Mathias Nelle, Benedikt Bubl, Walter Bär, Brigitte Scharrer, Thomas Riedel, Jean-François Tolsa, Bjarte Rogdo, Irene Hoigne, André Birkenmaier, Giancarlo Natalucci, Angelika Berger, Alexandra Thajer
Journal: JAMA Network Open (2022)

Importance Intraventricular hemorrhage (IVH) is a major cause of neonatal morbidity and mortality in preterm infants without a specific medical treatment to date. Objective To assess the safety and short-term outcomes of high-dose erythropoietin in preterm infants with IVH. Design, Setting, and Participants Between April 1, 2014, and August 3, 2018, a randomized double-blind clinical trial enrolled 121 preterm infants (gestational age &amp;amp;lt;32 weeks or birth weight &amp;amp;lt;1500 g) aged 8 or less days with moderate to severe IVH identified by cerebral ultrasonography from 8 Swiss and Austrian tertiary neonatal units. Statistical analyses were performed between October 1, 2019, and September 12, 2022. Interventions Infants received intravenous high-dose erythropoietin (2000 units/kg body weight) or placebo at 4 time points between weeks 1 and 4 of life. Main Outcomes and Measures Secondary outcomes included (1) mortality and morbidity rates and (2) brain magnetic resonance imaging findings at term-equivalent age (TEA). The primary outcome was the composite intelligence quotient at 5 years of age (not available before 2023). Results Sixty infants (48% male [n = 29]) were randomly assigned to receive erythropoietin, and 61 infants (61% male [n = 37]) were randomly assigned to receive placebo. The median birth weight was 832 g (IQR, 687-990 g) in the erythropoietin group and 870 g (IQR, 680-1110 g) in the placebo group. Median gestation was 26.1 weeks (IQR, 24.8-27.3 weeks) in the erythropoietin group and 27.0 weeks (24.9–28.1 weeks) in the placebo group. The 2 groups had similar baseline characteristics and morbidities. Up to TEA, 10 newborns died (16.7%) in the erythropoietin group, and 5 newborns (8.2%) died in the placebo group (adjusted odds ratio, 2.24 [95% CI, 0.74-7.66]; P = .15). Infants receiving erythropoietin had higher mean hematocrit levels. Conventional magnetic resonance imaging at TEA for 100 infants showed no significant differences in global or regional brain injury scores. Conclusions and Relevance This preliminary report of a randomized clinical trial found no evidence that high-dose erythropoietin in preterm infants with IVH affects brain injury scores on conventional magnetic resonance imaging at TEA. Higher mortality in the erythropoietin group was not significant but should be reassessed based on future results from similar trials. Trial Registration ClinicalTrials.gov Identifier: NCT02076373
Continuous Indexing of Fibrosis (CIF): improving the assessment and classification of MPN patients
Authors: Hosuk Ryou, Korsuk Sirinukunwattana, Alan Aberdeen, Gillian Grindstaff, Bernadette J. Stolz, Helen Byrne, Heather A. Harrington, Nikolaos Sousos, Anna L. Godfrey, Claire N. Harrison, Bethan Psaila, Adam J. Mead, Gabrielle Rees, Gareth D. H. Turner, Jens Rittscher, Daniel Royston
Journal: Leukemia (2022)

The grading of fibrosis in myeloproliferative neoplasms (MPN) is an important component of disease classification, prognostication and monitoring. However, current fibrosis grading systems are only semi-quantitative and fail to fully capture sample heterogeneity. To improve the quantitation of reticulin fibrosis, we developed a machine learning approach using bone marrow trephine (BMT) samples (n = 107) from patients diagnosed with MPN or a reactive marrow. The resulting Continuous Indexing of Fibrosis (CIF) enhances the detection and monitoring of fibrosis within BMTs, and aids MPN subtyping. When combined with megakaryocyte feature analysis, CIF discriminates between the frequently challenging differential diagnosis of essential thrombocythemia (ET) and pre-fibrotic myelofibrosis with high predictive accuracy [area under the curve = 0.94]. CIF also shows promise in the identification of MPN patients at risk of disease progression; analysis of samples from 35 patients diagnosed with ET and enrolled in the Primary Thrombocythemia-1 trial identified features predictive of post-ET myelofibrosis (area under the curve = 0.77). In addition to these clinical applications, automated analysis of fibrosis has clear potential to further refine disease classification boundaries and inform future studies of the micro-environmental factors driving disease initiation and progression in MPN and other stem cell disorders.
PET/CT Showing a Case of Langerhans Cell Histiocytosis Involving the Pleura
Authors: Pan Tang, Yushan Zhou, Rong Tian
Journal: Clinical Nuclear Medicine (2022)

We describe a case of Langerhans cell histiocytosis involving the bilateral pleura on FDG PET/CT. Multiple pleural nodules were detected by CT in a 38-year-old woman with chest pain and night sweats. Malignant tumors were suspected. PET/CT showed abnormal FDG uptake in those pleural lesions. No other abnormal foci were seen in the rest of the whole body. A primary pleural disease was considered. Then the histopathologic findings after biopsy confirmed the diagnosis of Langerhans cell histiocytosis.
Comparative Effectiveness of Team-Based Care With and Without a Clinical Decision Support System for Diabetes Management
Authors: Xiulin Shi, Jiang He, Mingzhu Lin, Changqin Liu, Bing Yan, Haiqu Song, Caihong Wang, Fangsen Xiao, Peiying Huang, Liying Wang, Zhibin Li, Yinxiang Huang, Mulin Zhang, Chung-Shiuan Chen, Katherine Obst, Lizheng Shi, Weihua Li, Shuyu Yang, Guanhua Yao, Xuejun Li
Journal: Annals of Internal Medicine (2022)

Uncontrolled hyperglycemia, hypercholesterolemia, and hypertension are common in persons with diabetes.To compare the effectiveness of team-based care with and without a clinical decision support system (CDSS) in controlling glycemia, lipids, and blood pressure (BP) among patients with type 2 diabetes.Cluster randomized trial. (ClinicalTrials.gov: NCT02835287).38 community health centers in Xiamen, China.11 132 persons aged 50 years or older with uncontrolled diabetes and comorbid conditions, 5475 receiving team-based care with a CDSS and 5657 receiving team-based care alone.Team-based care was delivered by primary care physicians, health coaches, and diabetes specialists in all centers. In addition, a computerized CDSS, which generated individualized treatment recommendations based on clinical guidelines, was implemented in 19 centers delivering team-based care with a CDSS.Coprimary outcomes were mean reductions in hemoglobin A1c (HbA1c) level, low-density lipoprotein cholesterol (LDL-C) level, and systolic BP over 18 months and the proportion of participants with all 3 risk factors controlled at 18 months.During the 18-month intervention, HbA1c levels, LDL-C levels, and systolic BP significantly decreased by -0.9 percentage point (95% CI, -0.9 to -0.8 percentage point), -0.49 mmol/L (CI, -0.53 to -0.45 mmol/L) (-19.0 mg/dL [CI, -20.4 to -17.5 mg/dL]), and -9.1 mm Hg (CI, -9.9 to -8.3 mm Hg), respectively, in team-based care with a CDSS and by -0.6 percentage point (CI, -0.7 to -0.5 percentage point), -0.32 mmol/L (CI, -0.35 to -0.29 mmol/L) (-12.5 mg/dL [CI, -13.6 to -11.3 mg/dL]), and -7.5 mm Hg (CI, -8.4 to -6.6 mm Hg), respectively, in team-based care alone. Net differences were -0.2 percentage point (CI, -0.3 to -0.1 percentage point) for HbA1c level, -0.17 mmol/L (CI, -0.21 to -0.12 mmol/L) (-6.5 mg/dL [CI, -8.3 to -4.6 mg/dL]) for LDL-C level, and -1.5 mm Hg (CI, -2.8 to -0.3 mm Hg) for systolic BP. The proportion of patients with controlled HbA1c, LDL-C, and systolic BP was 16.9% (CI, 15.7% to 18.2%) in team-based care with a CDSS and 13.0% (CI, 11.7% to 14.3%) in team-based care alone.There was no usual care control, and clinical outcome assessors were unblinded; the analysis did not account for multiple comparisons.Compared with team-based care alone, team-based care with a CDSS significantly reduced cardiovascular risk factors in patients with diabetes, but the effect was modest.Xiamen Municipal Health Commission.
T cells of colorectal cancer patients’ stimulated by neoantigenic and cryptic peptides better recognize autologous tumor cells
Authors: Sandra Schwarz, Johanna Schmitz, Markus W Löffler, Michael Ghosh, Hans-Georg Rammensee, Evgenia Olshvang, Marvin Markel, Nadine Mockel-Tenbrinck, Andrzej Dzionek, Susann Krake, Basak Arslan, Kapil Dev Kampe, Anne Wendt, Peter Bauer, Christina S Mullins, Andreas Schlosser, Michael Linnebacher
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Patients with cancers that exhibit extraordinarily high somatic mutation numbers are ideal candidates for immunotherapy and enable identifying tumor-specific peptides through stimulation of tumor-reactive T cells (Tc). Methods Colorectal cancers (CRC) HROC113 and HROC285 were selected based on high TMB, microsatellite instability and HLA class I expression. Their HLA ligandome was characterized using mass spectrometry, compared with the HLA ligand atlas and HLA class I-binding affinity was predicted. Cryptic peptides were identified using Peptide-PRISM. Patients’ Tc were isolated from either peripheral blood (pTc) or tumor material (tumor-infiltrating Tc, TiTc) and expanded. In addition, B-lymphoblastoid cells (B-LCL) were generated and used as antigen-presenting cells. pTc and TiTc were stimulated twice for 7 days using peptide pool-loaded B-LCL. Subsequently, interferon gamma (IFNγ) release was quantified by ELISpot. Finally, cytotoxicity against autologous tumor cells was assessed in a degranulation assay. Results 100 tumor-specific candidate peptides—97 cryptic peptides and 3 classically mutated neoantigens—were selected. The neoantigens originated from single nucleotide substitutions in the genes IQGAP1, CTNNB1, and TRIT1 . Cryptic and neoantigenic peptides inducing IFNγ secretion of Tc were further investigated. Stimulation of pTc and TiTc with neoantigens and selected cryptic peptides resulted in increased release of cytotoxic granules in the presence of autologous tumor cells, substantiating their improved tumor cell recognition. Tetramer staining showed an enhanced number of pTc and TiTc specific for the IQGAP1 neoantigen. Subpopulation analysis prior to peptide stimulation revealed that pTc mainly consisted of memory Tc, whereas TiTc constituted primarily of effector and effector memory Tc. This allows to infer that TiTc reacting to neoantigens and cryptic peptides must be present within the tumor microenvironment. Conclusion These results prove that the analyzed CRC present both mutated neoantigenic and cryptic peptides on their HLA class I molecules. Moreover, stimulation with these peptides significantly strengthened tumor cell recognition by Tc. Since the overall number of neoantigenic peptides identifiable by HLA ligandome analysis hitherto is small, our data emphasize the relevance of increasing the target scope for cancer vaccines by the cryptic peptide category.
In situ vaccination with cowpea mosaic virus elicits systemic antitumor immunity and potentiates immune checkpoint blockade
Authors: Chenkai Mao, Veronique Beiss, Gregory W Ho, Jennifer Fields, Nicole F Steinmetz, Steven Fiering
Journal: Journal for ImmunoTherapy of Cancer (2022)

In situ vaccination (ISV) is a cancer immunotherapy strategy in which immunostimulatory reagents are introduced directly into a tumor to stimulate antitumor immunity both against the treated tumor and systemically against untreated tumors. Recently, we showed that cowpea mosaic virus (CPMV) is a potent multi-toll-like receptor (TLR) agonist with potent efficacy for treating tumors in mice and dogs by ISV. However, ISV with CPMV alone does not uniformly treat all mouse tumor models tested, however this can be overcome through strategic combinations. More insight is needed to delineate potency and mechanism of systemic antitumor immunity and abscopal effect.We investigated the systemic efficacy (abscopal effect) of CPMV ISV with a two-tumor mouse model using murine tumor lines B16F10, 4T1, CT26 and MC38. Flow cytometry identified changes in cell populations responsible for systemic efficacy of CPMV. Transgenic knockout mice and depleting antibodies validated the role of relevant candidate cell populations and cytokines. We evaluated these findings and engineered a multicomponent combination therapy to specifically target the candidate cell population and investigated its systemic efficacy, acquired resistance and immunological memory in mouse models.ISV with CPMV induces systemic antitumor T-cell-mediated immunity that inhibits growth of untreated tumors and requires conventional type-1 dendritic cells (cDC1s). Furthermore, using multiple tumor mouse models resistant to anti-programmed death 1 (PD-1) therapy, we tested the hypothesis that CPMV along with local activation of antigen-presenting cells with agonistic anti-CD40 can synergize and strengthen antitumor efficacy. Indeed, this combination ISV strategy induces an influx of CD8+ T cells, triggers regression in both treated local and untreated distant tumors and potentiates tumor responses to anti-PD-1 therapy. Moreover, serial ISV overcomes resistance to anti-PD-1 therapy and establishes tumor-specific immunological memory.These findings provide new insights into in situ TLR activation and cDC1 recruitment as effective strategies to overcome resistance to immunotherapy in treated and untreated tumors.
Free HIV self-test for identification and linkage to care of previously undetected HIV infection in men who have sex with men in England and Wales (SELPHI): an open-label, internet-based, randomised controlled trial
Authors: Alison J Rodger, Leanne McCabe, Andrew N Phillips, Fiona C Lampe, Fiona Burns, Denise Ward, Valerie Delpech, Peter Weatherburn, T Charles Witzel, Roger Pebody, Peter Kirwan, Michelle Gabriel, Jameel Khawam, Michael Brady, Kevin A Fenton, Roy Trevelion, Yolanda Collaco-Moraes, Sheena McCormack, David Dunn
Journal: The Lancet HIV (2022)
Association of circulating markers with cognitive decline after radiation therapy for brain metastasis
Authors: Kristin Huntoon, S Keith Anderson, Karla V Ballman, Erin Twohy, Katharine Dooley, Wen Jiang, Yi An, Jing Li, Christina von Roemeling, Yaqing Qie, Owen A Ross, Jane H Cerhan, Anthony C Whitton, Jeffrey N Greenspoon, Ian F Parney, Jonathan B Ashman, Jean-Paul Bahary, Constantinos Hadjipanayis, James J Urbanic, Elana Farace, Deepak Khuntia, Nadia N Laack, Paul D Brown, David Roberge, Betty Y S Kim
Journal: Neuro-Oncology (2022)

Abstract Background A recent phase III trial (NCT01372774) comparing use of stereotactic radiosurgery [SRS] versus whole-brain radiation therapy [WBRT] after surgical resection of a single brain metastasis revealed that declines in cognitive function were more common with WBRT than with SRS. A secondary endpoint in that trial, and the primary objective in this secondary analysis, was to identify baseline biomarkers associated with cognitive impairment after either form of radiotherapy for brain metastasis. Here we report our findings on APOE genotype and serum levels of associated proteins and their association with radiation-induced neurocognitive decline. Methods In this retrospective analysis of prospectively collected samples from a completed randomized clinical trial, patients provided blood samples every 3 months that were tested by genotyping and enzyme-linked immunosorbent assay, and results were analyzed in association with cognitive impairment. Results The APOE genotype was not associated with neurocognitive impairment at 3 months. However, low serum levels of ApoJ, ApoE, or ApoA protein (all P &amp;lt; .01) and higher amyloid beta (Aβ 1–42) levels (P = .048) at baseline indicated a greater likelihood of neurocognitive decline at 3 months after SRS, whereas lower ApoJ levels were associated with decline after WBRT (P = .014). Conclusions Patients with these pretreatment serum markers should be counseled about radiation-related neurocognitive decline.
A Time and Place for Inhibiting Autophagy
Authors: Boyi Gan
Journal: Cancer Research (2022)

Abstract Autophagy is an attractive therapeutic target in cancer. Successful autophagy-focused clinical intervention will require a detailed understanding of when and where autophagy is important during tumorigenesis. In this issue of Cancer Research, Khayati and colleagues use state-of-the-art genetically engineered mouse models to demonstrate that transient systemic inhibition of autophagy can irreversibly impair the growth of established lung tumors with a good tolerability in normal tissues, suggesting a therapeutic strategy for cancer treatment. See related article by Khayati et al., p. 4429
The best game in town: The reemergence of the language-of-thought hypothesis across the cognitive sciences
Authors: Jake Quilty-Dunn, Nicolas Porot, Eric Mandelbaum
Journal: Behavioral and Brain Sciences (2022)

Mental representations remain the central posits of psychology after many decades of scrutiny. However, there is no consensus about the representational format(s) of biological cognition. This paper provides a survey of evidence from computational cognitive psychology, perceptual psychology, developmental psychology, comparative psychology, and social psychology, and concludes that one type of format that routinely crops up is the language-of-thought (LoT). We outline six core properties of LoTs: (i) discrete constituents; (ii) role-filler independence; (iii) predicate-argument structure; (iv) logical operators; (v) inferential promiscuity; and (vi) abstract content. These properties cluster together throughout cognitive science. Bayesian computational modeling, compositional features of object perception, complex infant and animal reasoning, and automatic, intuitive cognition in adults all implicate LoT-like structures. Instead of regarding LoT as a relic of the previous century, researchers in cognitive science and philosophy-of-mind must take seriously the explanatory breadth of LoT-based architectures. We grant that the mind may harbor many formats and architectures, including iconic and associative structures as well as deep-neural-network-like architectures. However, as computational/representational approaches to the mind continue to advance, classical compositional symbolic structures - that is, LoTs - only prove more flexible and well-supported over time.
In older men, an invitation for comprehensive CV screening did not reduce death at 5.6 y
Authors: Konstantin A. Krychtiuk, Christopher B. Granger
Journal: Annals of Internal Medicine (2022)

ACP Journal ClubDecember 2022In older men, an invitation for comprehensive CV screening did not reduce death at 5.6 yKonstantin A. Krychtiuk, MD, PhD, Christopher B. Granger, MDKonstantin A. Krychtiuk, MD, PhDDuke Clinical Research Institute, Durham, North Carolina, USA (K.A.K., C.B.G.)Search for more papers by this author, Christopher B. Granger, MDDuke Clinical Research Institute, Durham, North Carolina, USA (K.A.K., C.B.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/J22-0098 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationLindholt JS, Søgaard R, Rasmussen LM, et al. Five-year outcomes of the Danish Cardiovascular Screening (DANCAVAS) trial. N Engl J Med. 2022;387:1385-94. https://pubmed.ncbi.nlm.nih.gov/36027560Clinical Impact RatingsGIM/FP/GP: Cardiology: Geriatrics: Reference1. Visseren FLJ, Mach F, Smulders YM, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021;42:3227-337. [PMID: 34458905] Google Scholar Author, Article, and Disclosure InformationAffiliations: Duke Clinical Research Institute, Durham, North Carolina, USA (K.A.K., C.B.G.)Disclosures: The commentators have reported no disclosures of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J22-0098.This article was published at Annals.org on 6 December 2022.ACP Journal Club is editorially independent from Annals of Internal Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics December 2022Volume 175, Issue 12Page: JC140KeywordsClinical trialsComputed axial tomographyHealth screeningHeartMortalityPopulation statisticsRandomized trialsTreatment guidelinesVascular diseases ePublished: 6 December 2022 Issue Published: December 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Genetics in non-alcoholic fatty liver disease: The role of risk alleles through the lens of immune response
Authors: Silvia Sookoian, Carlos J. Pirola
Journal: Clinical and Molecular Hepatology (2022)

The knowledge on the genetic component of non-alcoholic fatty liver disease (NAFLD) has grown exponentially over the last 10 to 15 years. This review summarizes the current evidence and the latest developments in the genetics of NAFLD and non-alcoholic steatohepatitis (NASH) from the immune system’s perspective. Activation of innate and or adaptive immune response is an essential driver of NAFLD disease severity and progression. Lipid and immune pathways are crucial in the pathophysiology of NAFLD and NASH. Here, we highlight novel applications of genomic techniques, including single-cell sequencing and the genetics of gene expression, to elucidate the potential involvement of NAFLD/NASH-risk alleles in modulating immune system cells. Together, our focus is to provide an overview of the potential involvement of the NAFLD/NASH-related risk variants in mediating the immune-driven liver disease severity and diverse systemic pleiotropic effects.
64Cu-DOTATATE Uptake in a Pulmonary Hamartoma
Authors: Hong Song, Kip E. Guja, Eric J. Yang, Haiwei Henry Guo
Journal: Clinical Nuclear Medicine (2022)

DOTATATE PET/CT is frequently used to evaluate indeterminant pulmonary nodules suspected to be pulmonary carcinoid. We report an unexpected case of pulmonary hamartoma demonstrating 64Cu-DOTATATE uptake in a 43-year-old woman with a slowly enlarging pulmonary nodule. Histopathological staining showed somatostatin receptor 2 expression on vascular endothelial cells and a proportion of cartilage and smooth muscle cells within the hamartoma.
Incidental Detection of a Type B3 Thymoma on 68Ga-FAPI-04 PET/CT Imaging
Authors: Ferat Kepenek, Cihan Gündoğan, İhsan Kaplan, Nilgün Söğütçü, Canan Can
Journal: Clinical Nuclear Medicine (2022)

18F-FDG PET/CT performed for staging of colon cancer in a 60-year-old woman revealed a thymic neoplasm with increased radiopharmaceutical uptake in the anterior mediastinum. 68Ga-FAPI PET/CT showed low FAPI uptake in the anterior mediastinal mass. The patient was diagnosed with type B3 thymoma by histopathologic evaluation. In this case, thymoma demonstrated lower uptake with FAPI than FDG. Larger studies are required for the differentiation of malignant and benign mediastinal masses with FAPI.
Ammonia detoxification promotes CD8+ T cell memory development by urea and citrulline cycles
Authors: Ke Tang, Huafeng Zhang, Jinghui Deng, Dianheng Wang, Shichuan Liu, Shuya Lu, Qingfa Cui, Chen Chen, Jincheng Liu, Zhuoshun Yang, Yonggang Li, Jie Chen, Jiadi Lv, Jingwei Ma, Bo Huang
Journal: Nature Immunology (2022)